The objective of the proposed investigation is to define the degradative pathway of the glycosaminoglucuronoglycan (acid mucopolysaccharide), dermatan sulfate. Mucopolysaccharides labeled biosynthetically with a radioactive tracer will be treated with a series of enzymes to leave dermatan sulfate as the only macromolecule. This will serve as putative substrate for examination of the degradative pathway of this mucopolysaccharide. Each enzyme necessary for hydrolyzing each known residue of the dermatan sulfate structure will be isolated and purified from the others. They will then be combined to provide a functionally competent degradative system, free of interfering constituents. The selection of enzymes will be guided by recent discoveries on enzyme defects associated with the mucopolysaccharidoses. The ordered sequence of reactions for dermatan sulfate degradation will be mapped by employing enzymes in various combinations. Mucopolysaccharide catabolism is involved in a wide spectrum of normal and pathological processes and these studies will be of value in several major areas of biomedical research including the genetic mucopolysaccharidoses, cystic fibrosis and rheumatoid arthritis. It is a truism that the elucidation of normal metabolic events must precede any real understanding of pathological conditions. Such knowledge should enhance the development of early diagnostic procedures and form the basis for rational therapeutic and prophylactic treatment.